G-quadruplex DNA structure is a positive regulator of MYC transcription.

DNA structure can regulate genome function. Four-stranded DNA G-quadruplex (G4) structures have been implicated in transcriptional regulation; however, previous studies have not directly addressed the role of an individual G4 within its endogenous cellular context. Using CRISPR to genetically abrogate endogenous G4 structure folding, we directly interrogate the G4 found within the upstream regulatory region of the critical human MYC oncogene. G4 loss leads to suppression of MYC transcription from the P1 promoter that is mediated by the deposition of a de novo nucleosome alongside alterations in RNA polymerase recruitment. We also show that replacement of the endogenous MYC G4 with a different G4 structure from the KRAS oncogene restores G4 folding and MYC transcription. Moreover, we demonstrate that the MYC G4 structure itself, rather than its sequence, recruits transcription factors and histone modifiers. Overall, our work establishes that G4 structures are important features of transcriptional regulation that coordinate recruitment of key chromatin proteins and the transcriptional machinery through interactions with DNA secondary structure, rather than primary sequence.

SERS analysis of cancer cell-secreted purines reveals a unique paracrine crosstalk in MTAP-deficient tumors.

The tumor microenvironment (TME) is a dynamic pseudoorgan that shapes the development and progression of cancers. It is a complex ecosystem shaped by interactions between tumor and stromal cells. Although the traditional focus has been on the paracrine communication mediated by protein messengers, recent attention has turned to the metabolic secretome in tumors. Metabolic enzymes, together with exchanged substrates and products, have emerged as potential biomarkers and therapeutic targets. However, traditional techniques for profiling secreted metabolites in complex cellular contexts are limited. Surface-enhanced Raman scattering (SERS) has emerged as a promising alternative due to its nontargeted nature and simplicity of operation. Although SERS has demonstrated its potential for detecting metabolites in biological settings, its application in deciphering metabolic interactions within multicellular systems like the TME remains underexplored. In this study, we introduce a SERS-based strategy to investigate the secreted purine metabolites of tumor cells lacking methylthioadenosine phosphorylase (MTAP), a common genetic event associated with poor prognosis in various cancers. Our SERS analysis reveals that MTAP-deficient cancer cells selectively produce methylthioadenosine (MTA), which is taken up and metabolized by fibroblasts. Fibroblasts exposed to MTA exhibit: i) molecular reprogramming compatible with cancer aggressiveness, ii) a significant production of purine derivatives that could be readily recycled by cancer cells, and iii) the capacity to secrete purine derivatives that induce macrophage polarization. Our study supports the potential of SERS for cancer metabolism research and reveals an unprecedented paracrine crosstalk that explains TME reprogramming in MTAP-deleted cancers.

Mast cell infiltration of the choroid and protease release are early events in age-related macular degeneration associated with genetic risk at both chromosomes 1q32 and 10q26.

Age-related macular degeneration (AMD) is a leading cause of visual loss. It has a strong genetic basis, and common haplotypes on chromosome (Chr) 1 (CFH Y402H variant) and on Chr10 (near HTRA1/ARMS2) contribute the most risk. Little is known about the early molecular and cellular processes in AMD, and we hypothesized that analyzing submacular tissue from older donors with genetic risk but without clinical features of AMD would provide biological insights. Therefore, we used mass spectrometry­based quantitative proteomics to compare the proteins in human submacular stromal tissue punches from donors who were homozygous for high-risk alleles at either Chr1 or Chr10 with those from donors who had protective haplotypes at these loci, all without clinical features of AMD. Additional comparisons were made with tissue from donors who were homozygous for high-risk Chr1 alleles and had early AMD. The Chr1 and Chr10 risk groups shared common changes compared with the low-risk group, particularly increased levels of mast cell­specific proteases, including tryptase, chymase, and carboxypeptidase A3. Histological analyses of submacular tissue from donors with genetic risk of AMD but without clinical features of AMD and from donors with Chr1 risk and AMD demonstrated increased mast cells, particularly the tryptase-positive/chymase-negative cells variety, along with increased levels of denatured collagen compared with tissue from low­genetic risk donors. We conclude that increased mast cell infiltration of the inner choroid, degranulation, and subsequent extracellular matrix remodeling are early events in AMD pathogenesis and represent a unifying mechanistic link between Chr1- and Chr10-mediated AMD.

Longer time to testosterone recovery impacts favorably on outcomes for prostate cancer following androgen deprivation and radiotherapy.

PURPOSE: To evaluate the impact of sustained hypogonadism after androgen deprivation therapy (ADT) associated with radiotherapy in prostate cancer (PCa) patients with biochemical relapse-free survival (bRFS). METHODS: A retrospective cohort analysis of 213 consecutive PCa patients referred for radiotherapy plus ADT was carried out. Follow-up times including time to testosterone recovery (TTR) and bRFS were calculated from the end of ADT. Univariate and multivariate Cox regression analyses predicting bRFS were used. The optimal cutoffs for TTR and duration of ADT were determined using the maximally selected rank statistics (MSRS). RESULTS: After a median follow-up of 104 months, 18 patients relapsed among those who had recovered testosterone levels and 9 among those who did not. Median ADT duration was 36 months. The optimal cutoff for TTR was determined using MSRS. TTR >48 months was significantly associated with better bRFS (logrank, p < 0.0027). Five-year bRFS was 100% for >48 months vs. 85% for <48 months. TTR was the only significant variable for bRFS in multivariate Cox analysis. CONCLUSION: Our data show an association between longer TTR and bRFS values among PCa patients treated with ADT.

Safety Profile and Effectiveness of Dapagliflozin in Pediatric Patients with Chronic Kidney Disease.

INTRODUCTION: Nephroprotection in pediatric chronic kidney disease (CKD) has a major positive impact, both on residual renal function and on quality of life, by delaying the need for renal replacement therapy. To this day, nephroprotective drugs used in children are mainly limited to angiotensin-converting enzyme (ACE) inhibitors and angiotensin-receptor blockers; interestingly, as suggested by trials conducted in adults with CKD, sodium-glucose cotransporter 2 inhibitors (SGLT2i) might also be beneficial to pediatric patients. However, there are no validated data to this date documenting the effect of SGLT2i in pediatric patients with CKD. METHODS: We present a retrospective single-center study reporting the use of dapagliflozin in pediatric patients with CKD, aiming to evaluate dapagliflozin safety profile as well as its potential for renal protection. Our study describes 7 patients with a mean age of 13.3 years (+/- 7.029) presenting with identified glomerulopathy, leading to CKD and already treated by ACE inhibitors. Patients received a daily dose of dapagliflozin of 5 or 10 mg. RESULTS: Over a period of 15 months, all patients reported the medication as easy to use. After an initial dip, estimated glomerular filtration rate decline slope stabilized in all patients. Urinary albumin-over-creatinine ratio had a strong tendency to decrease after 6 months of treatment (p = 0.0684). Systolic blood pressure also had a tendency to decrease after 6 months of treatment (p = 0.1). No significant side effect was reported by the patients. CONCLUSION: The promising results presented in this study support the use of SGLT2i in pediatric patients with CKD, although larger, randomized controlled trials in pediatric patients are necessary to better characterize their effectiveness in this particular population.

Impact of nirsevimab prophylaxis on paediatric respiratory syncytial virus (RSV)-related hospitalisations during the initial 2023/24 season in Luxembourg.

After Luxembourg introduced nirsevimab immunisation against respiratory syncytial virus (RSV), estimated neonatal coverage was 84% (1,277 doses/1,524 births) in 2023. That year, paediatric RSV-related hospitalisations, especially concerning infants < 6 months old (n = 72) seemed to decrease compared to the same period in 2022 (n = 232). In 2023, hospitalised children's mean age increased (14.4 months vs 7.8 months in 2022; p < 0.001) and hospital-stay length decreased (3.2 days vs 5.1 days; p < 0.001). In infants < 6 months old, intensive-care unit admissions appeared to drop (n = 28 vs 9). This suggests that nirsevimab prophylaxis reduced severe RSV infections, particularly in infants < 6 months old, thereby alleviating healthcare strain.

[Pharmacological intervention in the medication review of institutionalised elderly patients under polypharmacy]. / Intervención farmacéutica en la revisión del tratamiento en pacientes mayores polimedicados institucionalizados.

OBJECTIVE: To describe the Drug-Related Problems (DRP) and their resolution after pharmacological review in institutionalised elderly patients under polypharmacy. DESIGN: Descriptive, retrospective cohort study from January to October of 2022. LOCATION: Twelve nursing homes at the Community of Madrid. PARTICIPANTS: 295 patients aged 65 or older taking at least 5 chronic medications prescribed prior to the treatment review. INTERVENTIONS: Medication reviews carried out by the pharmacist and agreed upon in face-to-face meetings between the primary care doctor, the nursing home doctor and the pharmacist. MAIN MEASUREMENTS: Detected DRP, types and resolution. A age, sex, and number of medications before and after the intervention. Pharmacological subgroups according to anatomical therapeutic chemical classification system (ATC) and active pharmaceutical ingredients involved in the detected DRPs. RESULTS: 1425 DRP were detected, with a mean of 4.85 (SD 3.33) DRPs/patient. The most frequent DRP was reconciliation error (32.52%), followed by pharmaceutical regimen and dosaje. Among the 1425 improvement proposals, 86.73% of them were accepted.Significant statistically differences were observed between the number of medications per patient prior to the pharmacotherapy review (12.29) and after it (10.20), obtaining an average difference of 2.09 (95%CI: 1.98-2.21; P<.001). CONCLUSIONS: It is found that the intervention of multidisciplinary team in which the pharmacist performs a revision of the medication decreased the number of prescribed medications. Therefore, it reduces polymedication and its associated risks.

LDR brachytherapy offers superior tumor control to single-fraction HDR prostate brachytherapy: A prospective study.

PURPOSE: To compare the clinical outcomes of single-fraction high-dose-rate (HDR) brachytherapy and single-fraction low-dose-rate (LDR) brachytherapy as the sole treatment for primary prostate cancer. MATERIAL AND METHODS: A quasi-randomized study that allocated, from March 2008 to February 2012, 129 low and intermediate risk prostate cancer patients to one single-fraction HDR of 19 Gy (61 patients) or to a 145 Gy 125 I LDR permanent implant (68 patients. Biochemical relapse-free survival (bRFS) and overall survival (OS) were compared using the Kaplan-Meier method and Cox regression analysis. RESULTS: After a median follow-up of 72 months in the HDR group, 26 patients relapsed, and after a median follow-up of 84 months in the LDR group, 7 patients relapsed (p < 0.0001). The 5-year bRFS was significantly better for the LDR group than for the HDR group (93.7% and 61.1%, respectively) (p < 0.0001). The 5-year OS also was significantly better in the LDR group (95.5% vs. 89.9%) (p = 0.0436). CONCLUSIONS: Permanent LDR prostate implant brachytherapy offers better clinical outcomes than single-fraction HDR for prostate cancer.

Machine Learning-Assisted High-Throughput SERS Classification of Cell Secretomes.

During the response to different stress conditions, damaged cells react in multiple ways, including the release of a diverse cocktail of metabolites. Moreover, secretomes from dying cells can contribute to the effectiveness of anticancer therapies and can be exploited as predictive biomarkers. The nature of the stress and the resulting intracellular responses are key determinants of the secretome composition, but monitoring such processes remains technically arduous. Hence, there is growing interest in developing tools for noninvasive secretome screening. In this regard, it has been previously shown that the relative concentrations of relevant metabolites can be traced by surface-enhanced Raman scattering (SERS), thereby allowing label-free biofluid interrogation. However, conventional SERS approaches are insufficient to tackle the requirements imposed by high-throughput modalities, namely fast data acquisition and automatized analysis. Therefore, machine learning methods were implemented to identify cell secretome variations while extracting standard features for cell death classification. To this end, ad hoc microfluidic chips were devised, to readily conduct SERS measurements through a prototype relying on capillary pumps made of filter paper, which eventually would function as the SERS substrates. The developed strategy may pave the way toward a faster implementation of SERS into cell secretome classification, which can be extended even to laboratories lacking highly specialized facilities.

A novel partial deletion of the TBL1XR1 gene detected using SNP array in a patient with motor delay, growth failure and Klinefelter syndrome.

INTRODUCTION: Co-existence pathogenic copy number variation with aneuploidy is a rare phenomenon. Whole TBL1XR1 gene deletions are described and associated with autosomal dominant intellectual development disorder-41 (#616944). However, the phenotypical expression of the TBL1XR1 partial deletion is poorly described. CASE PRESENTATION: We describe the case of a male, aged 18 months, who presented delayed motor development, gait disturbance, mild generalized hypotonia, minor dysmorphic features and growth failure, in addition to Klinefelter syndrome (KS). The single nucleotide polymorphism array revealed the de novo pathogenic interstitial deletion of chromosome 3q26.32 of 202 kb size that encompassed the first two exons of one relevant coding gene: TBL1XR1 (*608628). CONCLUSION: We report a male without clinical signs of KS and overlapped phenotypical features with another TBL1XR1 related disease: Pierpont syndrome (#602342). This patient extends the phenotypic spectrum of TBL1XR1 gene pathogenic variants.

A Morbillivirus Infection Shifts DC Maturation Toward a Tolerogenic Phenotype to Suppress T Cell Activation.

Viruses have evolved numerous strategies to impair immunity so that they can replicate more efficiently. Among those, the immunosuppressive effects of morbillivirus infection can be particularly problematic, as they allow secondary infections to take hold in the host, worsening disease prognosis. In the present work, we hypothesized that the highly contagious morbillivirus peste des petits ruminants virus (PPRV) could target monocytes and dendritic cells (DC) to contribute to the immunosuppressive effects produced by the infection. Monocytes isolated from healthy sheep, a natural host of the disease, were able be infected by PPRV and this impaired the differentiation and phagocytic ability of immature monocyte-derived DC (MoDC). We also assessed PPRV capacity to infect differentiated MoDC. Ovine MoDC could be productively infected by PPRV, and this drastically reduced MoDC capacity to activate allogeneic T cell responses. Transcriptomic analysis of infected MoDC indicated that several tolerogenic DC signature genes were upregulated upon PPRV infection. Furthermore, PPRV-infected MoDC could impair the proliferative response of autologous CD4+ and CD8+ T cell to the mitogen concanavalin A (ConA), which indicated that DC targeting by the virus could promote immunosuppression. These results shed new light on the mechanisms employed by morbillivirus to suppress the host immune responses. IMPORTANCE Morbilliviruses pose a threat to global health given their high infectivity. The morbillivirus peste des petits ruminants virus (PPRV) severely affects small-ruminant-productivity and leads to important economic losses in communities that rely on these animals for subsistence. PPRV produces in the infected host a period of severe immunosuppression that opportunistic pathogens exploit, which worsens the course of the infection. The mechanisms of PPRV immunosuppression are not fully understood. In the present work, we demonstrate that PPRV can infect professional antigen-presenting cells called dendritic cells (DC) and disrupt their capacity to elicit an immune response. PPRV infection promoted a DC activation profile that favored the induction of tolerance instead of the activation of an antiviral immune response. These results shed new light on the mechanisms employed by morbilliviruses to suppress the immune responses.

Endoscopic removal of lumen-apposing metal stents - risk factors for stent embedment, complex removals, and adverse events: analysis from a multicenter prospective case series.

BACKGROUND: Removing lumen-apposing metal stents (LAMSs) may be difficult and even harmful, but these features have seldom been analyzed. We aimed to generate a comprehensive assessment of the feasibility and safety of LAMS retrieval procedures. METHODS: A prospective multicenter case series including all technically successfully deployed LAMSs between January 2019 and January 2020 that underwent endoscopic stent removal. All retrieval-related data were prospectively recorded using standardized telephone questionnaires as part of centralized follow-up that ended after stent removal had been performed. Multivariable logistic regression models assessed the potential risk factors for complex removal. RESULTS: For the 407 LAMSs included, removal was attempted in 158 (38.8 %) after an indwell time of 46.5 days (interquartile range [IQR] 31-70). The median (IQR) removal time was 2 (1-4) minutes. Removal was labelled as complex in 13 procedures (8.2 %), although advanced endoscopic maneuvers were required in only two (1.3 %). Complex removal risk factors were stent embedment (relative risk [RR] 5.84, 95 %CI 2.14-15.89; P = 0.001), over-the-wire deployment (RR 4.66, 95 %CI 1.60-13.56; P = 0.01), and longer indwell times (RR 1.14, 95 %CI 1.03-1.27; P = 0.01). Partial and complete embedment were observed in 14 (8.9 %) and five cases (3.2 %), respectively. The embedment rate during the first 6 weeks was 3.1 % (2/65), reaching 15.9 % (10/63) during the following 6 weeks (P = 0.02). The adverse event rate was 5.1 %, including seven gastrointestinal bleeds (5 mild, 2 moderate). CONCLUSIONS: LAMS removal is a safe procedure, mostly requiring basic endoscopic techniques attainable in conventional endoscopy rooms. Referral to advanced endoscopy units should be considered for stents with known embedment or long indwell times, which may require more technically demanding procedures.

Kctd13 deletion reduces synaptic transmission via increased RhoA.

Copy-number variants of chromosome 16 region 16p11.2 are linked to neuropsychiatric disorders and are among the most prevalent in autism spectrum disorders. Of many 16p11.2 genes, Kctd13 has been implicated as a major driver of neurodevelopmental phenotypes. The function of KCTD13 in the mammalian brain, however, remains unknown. Here we delete the Kctd13 gene in mice and demonstrate reduced synaptic transmission. Reduced synaptic transmission correlates with increased levels of Ras homolog gene family, member A (RhoA), a KCTD13/CUL3 ubiquitin ligase substrate, and is reversed by RhoA inhibition, suggesting increased RhoA as an important mechanism. In contrast to a previous knockdown study, deletion of Kctd13 or kctd13 does not increase brain size or neurogenesis in mice or zebrafish, respectively. These findings implicate Kctd13 in the regulation of neuronal function relevant to neuropsychiatric disorders and clarify the role of Kctd13 in neurogenesis and brain size. Our data also reveal a potential role for RhoA as a therapeutic target in disorders associated with KCTD13 deletion.

Light-Driven Tetra- and Octa-ß-substituted Cationic Zinc(II) Phthalocyanines for Eradicating Fusarium oxysporum Conidia.

Photodynamic inactivation (PDI) is an emerging therapeutic approach that can effectively inactivate diverse microbial forms, including vegetative forms and spores, while preserving host tissues and avoiding the development of resistance to the photosensitization procedure. This study evaluates the antifungal and sporicidal photodynamic activity of two water-soluble amphiphilic tetra- and octa-ß-substituted zinc(II) phthalocyanine (ZnPc) dyes with dimethylaminopyridinium groups at the periphery (ZnPcs 1, 2) and their quaternized derivatives (ZnPcs 1a, 2a). Tetra(1, 1a)- and octa(2, 2a)-ß-substituted zinc(II) phthalocyanines were prepared and assessed as photosensitizers (PSs) for their effects on Fusarium oxysporum conidia. Antimicrobial photoinactivation experiments were performed with each PS at 0.1, 1, 10, and 20 µM under white light irradiation at an irradiance of 135 mW·cm-2, for 60 min (light dose of 486 J·cm-2). High PDI efficiency was observed for PSs 1a, 2, and 2a (10 µM), corresponding to inactivation until the method's detection limit. PS 1 (20 µM) also achieved a considerable reduction of >5 log10 in the concentration of viable conidia. The quaternized PSs (1a, 2a) showed better PDI performance than the non-quaternized ones (1, 2), even at the low concentration of 1 µM, and a light dose of 486 J·cm-2. These cationic phthalocyanines are potent photodynamic drugs for antifungal applications due to their ability to effectively inactivate resistant forms, like conidia, with low concentrations and reasonable energy doses.

In Vitro Photoinactivation of Fusarium oxysporum Conidia with Light-Activated Ammonium Phthalocyanines.

Antimicrobial photodynamic therapy (aPDT) has been explored as an innovative therapeutic approach because it can be used to inactivate a variety of microbial forms (vegetative forms and spores) without causing significant damage to host tissues, and without the development of resistance to the photosensitization process. This study assesses the photodynamic antifungal/sporicidal activity of tetra- and octasubstituted phthalocyanine (Pc) dyes with ammonium groups. Tetra- and octasubstituted zinc(II) phthalocyanines (1 and 2) were prepared and tested as photosensitizers (PSs) on Fusarium oxysporum conidia. Photoinactivation (PDI) tests were conducted with photosensitizer (PS) concentrations of 20, 40, and 60 µM under white-light exposure at an irradiance of 135 mW·cm-2, applied during 30 and 60 min (light doses of 243 and 486 J·cm-2). High PDI efficiency corresponding to the inactivation process until the detection limit was observed for both PSs. The tetrasubstituted PS was the most effective, requiring the lowest concentration and the shortest irradiation time for the complete inactivation of conidia (40 µM, 30 min, 243 J·cm-2). Complete inactivation was also achieved with PS 2, but a longer irradiation time and a higher concentration (60 µM, 60 min, 486 J·cm-2) were necessary. Because of the low concentrations and moderate energy doses required to inactivate resistant biological forms such as fungal conidia, these phthalocyanines can be considered potent antifungal photodynamic drugs.

Expression of Non-T Cell Activation Linker (NTAL) in Jurkat Cells Negatively Regulates TCR Signaling: Potential Role in Rheumatoid Arthritis.

T lymphocytes are key players in adaptive immune responses through the recognition of peptide antigens through the T Cell Receptor (TCR). After TCR engagement, a signaling cascade is activated, leading to T cell activation, proliferation, and differentiation into effector cells. Delicate control of activation signals coupled to the TCR is needed to avoid uncontrolled immune responses involving T cells. It has been previously shown that mice deficient in the expression of the adaptor NTAL (Non-T cell activation linker), a molecule structurally and evolutionarily related to the transmembrane adaptor LAT (Linker for the Activation of T cells), develop an autoimmune syndrome characterized by the presence of autoantibodies and enlarged spleens. In the present work we intended to deepen investigation into the negative regulatory functions of the NTAL adaptor in T cells and its potential relationship with autoimmune disorders. For this purpose, in this work we used Jurkat cells as a T cell model, and we lentivirally transfected them to express the NTAL adaptor in order to analyze the effect on intracellular signals associated with the TCR. In addition, we analyzed the expression of NTAL in primary CD4+ T cells from healthy donors and Rheumatoid Arthritis (RA) patients. Our results showed that NTAL expression in Jurkat cells decreased calcium fluxes and PLC-γ1 activation upon stimulation through the TCR complex. Moreover, we showed that NTAL was also expressed in activated human CD4+ T cells, and that the increase of its expression was reduced in CD4+ T cells from RA patients. Our results, together with previous reports, suggest a relevant role for the NTAL adaptor as a negative regulator of early intracellular TCR signaling, with a potential implication in RA.

Digital holography-based 3D particle localization for single-molecule tweezer techniques.

We present a three-dimensional (3D) imaging technique for the fast tracking of microscopic objects in a fluid environment. Our technique couples digital holographic microscopy with three-dimensional localization via parabolic masking. Compared with existing approaches, our method reconstructs 3D volumes from single-plane images, which greatly simplifies image acquisition, reduces the demand on microscope hardware, and facilitates tracking higher densities of microscopic particles while maintaining similar levels of precision. We demonstrate utility of this method in magnetic tweezer experiments, opening their use to multiplexed single-molecule force spectroscopy assays, which were previously limited by particle crowding and fast dissociation times. We propose that our technique will also be useful in other applications that involve the tracking of microscopic objects in three dimensions, such as studies of microorganism motility and 3D flow characterization of microfluidic devices.

Survival of Patient With Hemorrhagic Meningitis Associated With Inhalation Anthrax.

This report describes a 49-year-old male construction worker who acquired a Bacillus anthracis infection after working on a sheep farm. He experienced a severe respiratory infection, septic shock, and hemorrhagic meningoencephalitis with severe intracranial hypertension. After several weeks with multiple organ dysfunction syndrome, he responded favorably to antibiotic treatment. Three weeks into his hospitalization, an intracranial hemorrhage and cerebral edema led to an abrupt deterioration in his neurological status. A single dose of raxibacumab was added to his antimicrobial regimen on hospital day 27. His overall status, both clinical and radiographic, improved within a few days. He was discharged 2 months after admission and appears to have fully recovered.

The muon Smasher's guide.

We lay out a comprehensive physics case for a future high-energy muon collider, exploring a range of collision energies (from 1 to 100 TeV) and luminosities. We highlight the advantages of such a collider over proposed alternatives. We show how one can leverage both the point-like nature of the muons themselves as well as the cloud of electroweak radiation that surrounds the beam to blur the dichotomy between energy and precision in the search for new physics. The physics case is buttressed by a range of studies with applications to electroweak symmetry breaking, dark matter, and the naturalness of the weak scale. Furthermore, we make sharp connections with complementary experiments that are probing new physics effects using electric dipole moments, flavor violation, and gravitational waves. An extensive appendix provides cross section predictions as a function of the center-of-mass energy for many canonical simplified models.

Relationship between impulsivity, uncontrolled eating and body mass index: a hierarchical model.

BACKGROUND: Impulsivity increases the risk for obesity and weight gain. However, the precise role of impulsivity in the aetiology of overeating behavior and obesity is currently unknown. Here we examined the relationships between personality-related measures of impulsivity, Uncontrolled Eating, body mass index (BMI), and longitudinal weight changes. In addition, we analyzed the associations between general impulsivity domains and cortical thickness to elucidate brain vulnerability factors related to weight gain. METHODS: Students (N = 2318) in their first year of university-a risky period for weight gain-completed questionnaire measures of impulsivity and eating behavior at the beginning of the school year. We also collected their weight at the end of the term (N = 1177). Impulsivity was divided into three factors: stress reactivity, reward sensitivity and lack of self-control. Using structural equation models, we tested a hierarchical relationship, in which impulsivity traits were associated with Uncontrolled Eating, which in turn predicted BMI and weight change. Seventy-one participants underwent T1-weighted MRI to investigate the correlation between impulsivity and cortical thickness. RESULTS: Impulsivity traits showed positive correlations with Uncontrolled Eating. Higher scores in Uncontrolled Eating were in turn associated with higher BMI. None of the impulsivity-related measurements nor Uncontrolled Eating were correlated with longitudinal weight gain. Higher stress sensitivity was associated with increased cortical thickness in the superior temporal gyrus. Lack of self-control was positively associated with increased thickness in the superior medial frontal gyrus. Finally, higher reward sensitivity was associated with lower thickness in the inferior frontal gyrus. CONCLUSION: The present study provides a comprehensive characterization of the relationships between different facets of impulsivity and obesity. We show that differences in impulsivity domains might be associated with BMI via Uncontrolled Eating. Our results might inform future clinical strategies aimed at fostering self-control abilities to prevent and/or treat unhealthy weight gain.